Bellett R E, Mastrangelo M J, Laucius J F, Bodurtha A J
Cancer Treat Rep. 1976 May;60(5):595-600.
Fifty patients with metastatic malignant melanoma were randomized to treatment with either DTIC (2 mg/kg/day X 10 iv) or the combination of BCNU (150 mg/m2 iv) plus vincristine (VCR) (2 mg/m2 iv on Day 1 only). Treatment failures were crossed over to the alternate therapy. Primary, secondary, and cumulative response rates to DTIC were 29%, 9%, and 22%, respectively. Primary, secondary, and cumulative response rates to BCNU plus VCR were 23%, 29%, and 25%, respectively. Five of 26 patients (19%) experienced objective regression from secondary therapy after failure to respond to primary therapy. DTIC produced gastrointestinal and hematologic toxic effects; BCNU plus VCR produced gastrointestinal, hematologic, and neurologic toxic effects. VCR administered at a dose of 2 mg/m2 resulted in excessive neurologic toxic effects in 12 of 21 patients; a maximum VCR dose of 2 mg/injection was well tolerated by 15 subsequent patients without an adverse effect upon response rate. An analysis of tumor burden and organ involvement in responders and nonresponders suggests that DTIC is the first-choice treatment for patients with limited tumor burdens and nonvisceral metastases; BCNU plus VCR is the first-choice treatment for patients with extensive tumor burdens and visceral-predominant disease. However, failure to respond to primary therapy does not preclude response to secondary therapy with the alternate regimen.
50例转移性恶性黑色素瘤患者被随机分为两组，分别接受达卡巴嗪（2mg/kg/天，静脉注射，共10天）治疗或卡莫司汀（150mg/m²，静脉注射）加长春新碱（仅在第1天静脉注射2mg/m²）联合治疗。治疗失败的患者交叉接受替代疗法。达卡巴嗪的主要、次要和累积缓解率分别为29%、9%和22%。卡莫司汀加长春新碱的主要、次要和累积缓解率分别为23%、29%和25%。26例患者中有5例（19%）在对初始治疗无反应后，经二线治疗出现客观缓解。达卡巴嗪产生胃肠道和血液学毒性作用；卡莫司汀加长春新碱产生胃肠道、血液学和神经学毒性作用。以2mg/m²的剂量给予长春新碱时，21例患者中有12例出现过度的神经学毒性作用；随后的15例患者对2mg/次的最大长春新碱剂量耐受性良好，且缓解率未受不良反应影响。对缓解者和未缓解者的肿瘤负荷及器官受累情况进行分析表明，达卡巴嗪是肿瘤负荷有限且无内脏转移患者的首选治疗药物；卡莫司汀加长春新碱是肿瘤负荷广泛且以内脏为主疾病患者的首选治疗药物。然而，对初始治疗无反应并不排除对替代方案二线治疗有反应。
